Despite steady advances in treatment, coronary heart disease (CHD) remains the leading cause of death in American men and women, in part because many CHD events occur in individuals in whom the disease has not yet been identified. Well known risk factors such as hypertension, hypercholesterolemia, and smoking do not fully predict CHD risk, spurring intense interest in developing novel tests that could potentially improve risk stratification and targeting of primary prevention therapies. The goal of our proposed research is to assess the comparative effectiveness and cost-effectiveness of promising novel risk markers (e.g. high sensitivity C- reactive protein, calcium scoring, carotid intima media thickness) for the prevention of CHD. Specifically, by means of a decision and cost-effectiveness analysis based on current literature, we aim 1) To assess the comparative effectiveness of strategies utilizing novel risk markers for reclassifying individuals at intermediate risk and targeting primary prevention efforts. 2) To determine incremental cost-effectiveness ratios for routine testing with such markers in individuals deemed at intermediate risk by clinical risk stratification algorithms. This work will determine which of the proposed risk markers add best value in terms of targeting primary prevention efforts such as statin therapy and whether the additional costs of routine testing with such markers are justified by improved outcomes and possible cost savings in the future. These data will be critical to understanding the comparative effectiveness of these markers and focusing limited resources for future research, for example, through clinical trials of strategies including novel markers. PUBLIC HEALTH RELEVANCE: Prevention of coronary heart disease (CHD) is a major public health issue in the United States. No disease kills more Americans. Therefore, optimizing prevention efforts including healthy lifestyle choices and effective drug treatments is critically important and relevant to the public health. In this study, we will analyze whether additional blood based or imaging tests can add effectively to our ability to prevent CHD by targeting primary prevention efforts to those at highest risk and whether such testing can be performed at a reasonable cost to society when all the downstream results and costs of testing are factored in.